MUC1 carrying core 2 O-glycans functions as a molecular shield against NK cell attack, promoting bladder tumor metastasis.
MUC1 carrying core 2 O-glycans functions as a molecular shield against NK cell attack, promoting bladder tumor metastasis.
复制标题
DOI：
10.3892/ijo.2012.1411
复制
发表时间：
2012-06
影响因子：
5.2
通讯作者：
Tsuboi S
中科院分区：
文献类型：
--
作者：
Suzuki Y;Sutoh M;Hatakeyama S;Mori K;Yamamoto H;Koie T;Saitoh H;Yamaya K;Funyu T;Habuchi T;Arai Y;Fukuda M;Ohyama C;Tsuboi S
核心2 β-1，6-N-乙酰葡糖胺转移酶（C2 GnT）在细胞表面糖蛋白的O-聚糖（核心2 O-聚糖）中形成N-乙酰葡糖胺分支。表达C2 GnT的膀胱肿瘤通过在宿主血液循环中存活更长时间而获得高转移表型。然而，这种增加生存率的详细机制仍不清楚。在这项研究中，我们报告，C2 GnT在膀胱肿瘤中的表达与肿瘤进展呈正相关，膀胱肿瘤细胞表面粘蛋白1（MUC 1）携带核心2 O-聚糖在逃避自然杀伤（NK）细胞攻击中起着重要作用。在表达C2 GnT的膀胱肿瘤细胞中，高度核心2 O-糖基化的MUC 1在其O-聚糖中携带聚-N-乙酰乳糖胺，半乳糖凝集素-3通过该聚-N-乙酰乳糖胺与MUC 1结合。半乳糖凝集素-3与MUC 1核心2 O-聚糖中的聚-N-乙酰乳糖胺的结合减弱了肿瘤细胞与NK细胞的相互作用，并干扰了肿瘤坏死因子相关凋亡诱导配体进入肿瘤细胞表面。携带核心2 O-聚糖的MUC 1对NK细胞攻击的这些作用促进表达C2 GnT的肿瘤细胞逃避NK细胞免疫并在宿主血液循环中存活更长时间。我们揭示，MUC 1携带核心2 O-聚糖，因此作为一个分子盾牌对NK细胞的攻击，从而促进膀胱肿瘤转移。
Core 2 β-1,6-N-acetylglucosaminyltransferase (C2GnT) forms an N-acetylglucosamine branch in O-glycans (core 2 O-glycans) of cell surface glycoproteins. C2GnT-expressing bladder tumors acquire highly metastatic phenotypes by surviving longer in host blood circulation. However, the detailed mechanisms underlying this increased survival remain unclear. In this study, we report that the expression of C2GnT in bladder tumors positively correlates with tumor progression and that bladder tumor cell-surface mucin 1 (MUC1) carrying core 2 O-glycans plays an important role in the evasion from natural killer (NK) cell attack. In C2GnT-expressing bladder tumor cells, heavily core 2 O-glycosylated MUC1 carries poly-N-acetyllactosamine in its O-glycans and galectin-3 binds to MUC1 through this poly-N-acetyllactosamine. The binding of galectin-3 to poly-N-acetyllactosamine in MUC1 core 2 O-glycans attenuates the interaction of the tumor cells with NK cells and interferes with the access of tumor necrosis factor-related apoptosis-inducing ligand to the tumor cell surface. These effects of MUC1 carrying core 2 O-glycans on NK cell attack facilitate C2GnT-expressing tumor cells to evade NK cell immunity and survive longer in host blood circulation. We reveal that MUC1 carrying core 2 O-glycans thus functions as a molecular shield against NK cell attack, thereby promoting bladder tumor metastasis.
登录
查看更多内容
DOI：
10.1083/jcb.129.1.255
发表时间：
1995-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Wesseling J;van der Valk SW;Vos HL;Sonnenberg A;Hilkens J
通讯作者：
Hilkens J
影响因子：
82.9
作者：
Wagner, Klaus W.;Punnoose, Elizabeth A.;Ashkenazi, Avi
通讯作者：
Ashkenazi, Avi
影响因子：
11.2
作者：
Peng W;Wang HY;Miyahara Y;Peng G;Wang RF
通讯作者：
Wang RF
影响因子：
4.8
作者：
Argueso, Pablo;Guzman-Aranguez, Ana;Panjwani, Noorjahan
通讯作者：
Panjwani, Noorjahan
影响因子：
4.8
作者：
Tsuboi, S
通讯作者：
Tsuboi, S